Abstract: Real-Time Stereotactic Mass Spectrometry Tissue Analysis for Intraoperative Neurosurgical Guidance Clinical and Translational Research Abstract Gliomas account for 40% of intracranial tumors, with close to 70% of them being of anaplastic grade or higher. Their most malignant form, glioblastoma multiforme still resists elaborate treatment strategies with a median survival of 12-15 months, and 2 to 5 years for anaplastic gliomas. To this day, surgery remains the most important, and usually first treatment modality for the majority of brain tumors. The benefits of gross total tumor resection include relief of mass effect, decrease in risk for epilepsy, increase of time to progression, and increase survival time. It is now well accepted that a smaller volume of postoperative residual tumor is associated with an improved prognosis for the patient. The principal challenge and objective of neurosurgical intervention is therefore to maximize the resection of tumor, while minimizing the potential for neurological deficit by preserving critical tissue. Neurosurgeons must then have the capability during surgery to identify diseased tissue as well as critical brain tissue with the highest level of certitude. This project aims to integrate a combined mass spectrometry and neuronavigation platform into the clinical environment for in vivo measurement of tumor boundaries. Mass spectrometry derived signatures will be validated against standard histopathology and correlated to pre- and/or intra- operative radiology imaging. The molecular information could eventually be used to guide clinical decisions in the operating room. A further goal is to create portable tools that may be used in centers without the level of intraoperative imaging available in highly specialized centers. Combination of a novel mass spectrometry approach with a surgical probe will allow simultaneous surgical removal of tissue and in vivo molecular analysis. The proposed project will focus on glioma margin identification in real-time and integrate with a multimodality imaging platform to increase specificity in tumor boundaries detection, for the practice of personalized neurosurgical treatment. Public Health Relevance: In neurosurgical interventions for brain cancers, the principal challenge and objective is to maximize the resection of tumor, while minimizing the potential for neurological deficit by preserving critical tissue. This project aims to develop a real-time molecular analysis of the tissue at stake using mass spectrometry in combination with radiology imaging to guide neurosurgery. The platform being developed for such a complex system can be further adapted to other surgical interventions t in need of highly specific guidance.